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Actas Dermo-sifiliograficas 2014Although the first study on the efficacy of methotrexate in the treatment of psoriasis was reported in 1958, scientific evidence for this indication has been scant until... (Review)
Review
Although the first study on the efficacy of methotrexate in the treatment of psoriasis was reported in 1958, scientific evidence for this indication has been scant until quite recently. We now have new data on the pharmacokinetics and mechanism of action of methotrexate and new subcutaneous formulations that have improved the bioavailability, efficacy, and ease of administration of the drug. The results of recent clinical trials comparing methotrexate with several biologic agents have shown it to be the first-line therapy among the classic systemic treatments for psoriasis. Moreover, the incremental cost-effectiveness ratio for subcutaneous methotrexate has been shown to be superior to that of ciclosporin, adalimumab, and infliximab.
Topics: Dermatologic Agents; Humans; Methotrexate; Psoriasis
PubMed: 23434058
DOI: 10.1016/j.ad.2012.11.017 -
Biomedicine & Pharmacotherapy =... Jun 2022Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about forty years and to date MTX remains the part of global standard of treatment... (Review)
Review
Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about forty years and to date MTX remains the part of global standard of treatment for RA. The efficacy of MTX in RA is the result of multiple mechanisms of action. In order to summarize the possible pharmacological mechanisms of MTX in the treatment of RA, this review will elaborate on folate antagonism, promotion of adenosine accumulation, regulation of inflammatory signaling pathways, bone protection and maintenance of immune system function.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Methotrexate
PubMed: 35658215
DOI: 10.1016/j.biopha.2022.113074 -
Journal of Clinical Oncology : Official... Mar 2011Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and...
PURPOSE
Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and tolerability of pralatrexate, a novel antifolate with promising activity.
PATIENTS AND METHODS
Patients with independently confirmed PTCL who progressed following ≥ 1 line of prior therapy received pralatrexate intravenously at 30 mg/m(2)/wk for 6 weeks in 7-week cycles. Primary assessment of response was made by independent central review using the International Workshop Criteria. The primary end point was overall response rate. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS).
RESULTS
Of 115 patients enrolled, 111 were treated with pralatrexate. The median number of prior systemic therapies was three (range, 1 to 12). The response rate in 109 evaluable patients was 29% (32 of 109), including 12 complete responses (11%) and 20 partial responses (18%), with a median DoR of 10.1 months. Median PFS and OS were 3.5 and 14.5 months, respectively. The most common grade 3/4 adverse events were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%).
CONCLUSION
To our knowledge, PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma) is the largest prospective study conducted in patients with relapsed or refractory PTCL. Pralatrexate induced durable responses in relapsed or refractory PTCL irrespective of age, histologic subtypes, amount of prior therapy, prior methotrexate, and prior autologous stem-cell transplant. These data formed the basis for the US Food and Drug Administration approval of pralatrexate, the first drug approved for this disease.
Topics: Adult; Aged; Aged, 80 and over; Aminopterin; Drug Resistance, Neoplasm; Female; Folic Acid Antagonists; Humans; International Agencies; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Remission Induction; Salvage Therapy; Standard of Care; Survival Rate; Treatment Outcome; Young Adult
PubMed: 21245435
DOI: 10.1200/JCO.2010.29.9024 -
Hematology/oncology Clinics of North... Jun 2012This article focuses on the cellular, biochemical, and molecular pharmacology of antifolates and how a basic understanding of the mechanism of action of methotrexate,... (Review)
Review
This article focuses on the cellular, biochemical, and molecular pharmacology of antifolates and how a basic understanding of the mechanism of action of methotrexate, its cytotoxic determinants, mechanisms of resistance, and transport into and out of cells has led to the development of a new generation of antifolates, a process that continues in the laboratory and in the clinics. New approaches to folate-based cancer chemotherapy are described based on the targeted delivery of drugs to malignant cells.
Topics: Animals; Antimetabolites, Antineoplastic; Drug Resistance, Neoplasm; Folic Acid; Folic Acid Antagonists; Humans; Methotrexate; Molecular Targeted Therapy; Neoplasms
PubMed: 22520983
DOI: 10.1016/j.hoc.2012.02.002 -
Clinical Infectious Diseases : An... Jul 2021
Topics: Humans; Methotrexate
PubMed: 33170206
DOI: 10.1093/cid/ciaa1390 -
Deutsches Arzteblatt International Aug 2022
Topics: Humans; Methotrexate; Radiation Dosage
PubMed: 36422875
DOI: 10.3238/arztebl.m2022.0185 -
Fa Yi Xue Za Zhi Oct 2021
Topics: Female; Humans; Methotrexate; Pregnancy; Pregnancy, Ectopic
PubMed: 35191238
DOI: 10.12116/j.issn.1004-5619.2020.400330 -
The Korean Journal of Internal Medicine Nov 2018
Topics: Arthritis, Rheumatoid; Humans; Methotrexate; Polyethylene Glycols
PubMed: 30396253
DOI: 10.3904/kjim.2018.363 -
Dermatologic Clinics Oct 2015This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides,... (Review)
Review
This article reviews methotrexate and the more potent, related compound, pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis fungoides, Sézary syndrome, and CD30+ lymphoproliferative disorders. Although these folate antagonists are traditionally viewed as antiproliferative cell cycle inhibitors, it is recognized that they inhibit DNA methylation, providing a rationale for their use as epigenetic regulators and cell proliferation inhibitors. The underlying mechanisms are outlined, key supporting data presented, followed by brief mention of recent mathematical modeling supporting the general superiority of combination therapy. Several novel examples involving folate antagonists are proposed.
Topics: Aminopterin; Antimetabolites, Antineoplastic; Apoptosis; DNA Methylation; Epigenesis, Genetic; Folic Acid Antagonists; Humans; Lymphoma, T-Cell, Cutaneous; Methotrexate; S Phase; Skin Neoplasms
PubMed: 26433846
DOI: 10.1016/j.det.2015.05.009 -
CMAJ : Canadian Medical Association... Jan 2021
Topics: Female; Hand; Humans; Methotrexate; Middle Aged; Psoriasis
PubMed: 33667188
DOI: 10.1503/cmaj.200517-f